Excerpt from Migraine Headache

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Background

Although migraine is a term applied to certain headaches with a vascular quality, overwhelming evidence suggests that migraine is a dominantly inherited disorder characterized by varying degrees of recurrent vascular-quality headache, photophobia, sleep disruption, and depression.

See Medscape's Headache Resource Center for more information.

Pathophysiology

The mechanisms of migraine remain not completely understood. However, the advent of new technologies has allowed formulation of current concepts that may explain parts of the migraine syndrome. See also Pathophysiology and Treatment of Migraine and Related Headache.

Vascular theory

For many years, headache pain during a migraine attack was thought to be a reactive hyperemia in response to vasoconstriction-induced ischemia during aura. This explained the throbbing quality of the headache, its varied localization, and the relief obtained from ergots; however, it did not explain the prodrome and associated features, the efficacy of some drugs used to treat migraines that have no effect on blood vessels, and the fact that most patients do not have an aura.

Also, intracarotid and single-photon emission computed tomography (SPECT) studies revealed that the headache is dissociated from hyperperfusion at its onset and termination in patients suffering from migraine headache with aura. They also revealed that regional cerebral blood flow (rCBF) decreases in the posterior area of the relevant cerebral hemisphere even before the aura is noted and that headache occurred while rCBF remained decreased; rCBF gradually increased throughout the remainder of the headache phase. No consistent flow changes have been identified in patients suffering from migraine headache without aura, but rCBF remains normal in the majority. However, bilateral decrease in rCBF beginning at the occipital cortex and spreading anteriorly has been reported. More recently, Perciaccante has shown that migraine is characterized by a cardiac autonomic dysfunction.¹

Cortical spreading depression

The spread of hypoperfusion propagates at a speed similar to that of cortical spreading depression (CSD) and migraine aura. This suggests not only that CSD is the disturbance resulting in the clinical manifestation of migraine aura but also that this spreading oligemia can be clinically silent (ie, migraine without aura). Perhaps a certain threshold is required to produce symptoms in patients having aura but not in those without aura. CSD with or without clinical manifestation (aura) may be a key trigger for the headache of migraine. Although this question is unsettled, CSD has been postulated to directly excite trigeminovascular afferents by promoting release of nociceptive substances from neocortex into the interstitial space, causing direct firing of the nociceptive stimulus.

Vasoactive substances and neurotransmitters

Perivascular nerve activity also results in release of substances such as substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), and nitric oxide (NO), which interact with the blood vessel wall to produce dilatation, protein extravasation, and sterile inflammation, stimulating the trigeminocervical complex as shown by induction of c-fos antigen by positron emission tomography (PET) scan. Information then is relayed to the thalamus and cortex for registering of pain. Involvement of other centers may explain the associated autonomic symptoms and affective aspects of this pain.

Is the neurologically mediated sterile plasma extravasation the cause of this pain? Neurogenic plasma extravasation is inhibited by 5-HT1 agonists, GABA agonists, neurosteroids, prostaglandin inhibitors, SP antagonists, and the endothelin antagonist bosentan; the latter 2 are ineffective as antimigraine drugs, showing that blockade of neurogenic plasma extravasation is not completely predictive of antimigraine efficacy in humans. Neurogenically induced plasma extravasation may play a role in expression of pain in migraine, but whether this in itself is sufficient to cause pain is not clear; the presence of other stimulators may be required. Also, the pain process needs not only the activation of nociceptors of pain-producing intracranial structures but also reduction in the normal functioning of endogenous pain control pathways that gate the pain.

Migraine center

What generates a migraine episode? A potential "migraine center" in the brain stem has been proposed based on findings on PET of persistently elevated rCBF in the brain stem (ie, periaqueductal gray, midbrain reticular formation, locus ceruleus) even after sumatriptan produced resolution of headache and related symptoms in 9 patients who had experienced spontaneous attack of migraine without aura. This increased rCBF was not observed outside of the attack, suggesting that this activation is not due to pain perception or increased activity of the endogenous antinociceptive system.

That sumatriptan reversed the concomitant increased rCBF in the cerebral cortex but not the brainstem centers suggests dysfunction in the regulation involved in antinociception and vascular control of these centers. Thalamic processing of pain is known to be gated by ascending serotonergic fibers from the dorsal raphe nucleus and from aminergic nuclei in the pontine tegmentum as locus ceruleus and that the latter can alter brain flow and blood-brain barrier permeability. Perhaps when these modulatory controls are timed to dysfunction, the migrainous process ensues.

Frequency

United States

More than 23 million people in the United States suffer from migraine. This roughly corresponds to 17.6% of females and 6.0% of males.

Mortality/Morbidity

Headaches may serve as a warning: not all severe headaches are due to migraine; they can be a warning sign of more serious conditions. Headache characteristics that should raise concern include the following:

• Change in character of the headache over the time should raise a red flag. Headaches associated with other neurological signs or symptoms (eg, diplopia, loss of sensation, weakness, ataxia) or those of unusually abrupt onset.
• Headaches that are persistent (especially beyond 72 hours), that first occur after the age of 55 years, or that develop after head injury or major trauma. Headaches that are persistent on one side of the head (persistent one-sided throbbing headaches mimicking like migraines: arteriovenous malformation should be excluded with imaging).
• Headaches that are associated with stiff neck or fever
• Headaches without a clear family history of migraine headache

Race

The prevalence of migraine appears to be lower among African Americans and Asian Americans than among whites.

Sex

• Migraine headaches are reported to affect women more than men.
• Approximately 75% of all persons who experience migraines are women.

Age

• The prevalence of migraine appears to be similar for boys and girls in the prepubescent years.
• The prevalence of migraine is higher in adolescent girls than in boys of similar age.
• By early adulthood, migraine is 3 times as frequent in women as it is in men.

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